(3bq) Small Is Big: Tiny Theranostics Resolve Huge Biomedical Challenges Via a Drug-Free Approach, Current Contributions and Future Perspective

The heart of nanomedicine, nanoparticles, are envisioned to shift the paradigm of conventional medicine by furnishing the field with unprecedented properties. Nanoparticles can be applied simultaneously for the early detection, diagnosis and therapy to unravel the components, processes, and dynamics of diseases. The integration of diagnosis and therapy in tandem, known as ‘theranostic’, can tackle the conundrum of debilitating diseases such as cancer and infectious diseases. However, several obstacles slowed the translation of nanoparticle to the clinic such as batch to batch variation, the lack of control over cargo release, and particle instability.

An approach is pursued in my research where these challenges were circumvented by designing inherently therapeutic nanoparticles without the encapsulation of a secondary drug while being imageable by omnipresent imaging modalities (Figure 1). This universal approach has been demonstrated to be successful in multiscale to treat localized (dental biofilm, bone microdamage), and systemic diseases.

In this talk, I will elaborate on my research on the ‘Drug-Free Theranostic Approach to Combat Localized and Systemic Diseases using Nanoparticles’. My talk will showcase on the major areas of early detection and therapy for infectious disease, bone microdamage, and cancer using a material-driven approach via carbon dots and hafnium nanoparticles.

First, I will disclose my work on surface-modified nanoparticles as pathogenic bacteria- seeking probes (Biomaterials 2018). Oral biofilms can contribute to the host of diseases that compromise the quality of life and systemic health and incur economic costs such as bacterial pneumonia, diabetes mellitus, and atherosclerosis. In light of the many secondary complications and healthcare costs attributed to biofilm-associated diseases, early detection with conventional tools and intervention are necessary. The nanoparticles presented here were designed to detect the dental biofilm mass using conventional x-ray imaging in the dental clinic while suppressing the biofilm formation without secondary antibiotics in vivo. In the follow-up work (Advanced Materials 2019, Under review), I tweaked the composition of the nanoparticles using unique surface chemistry to target the pathological pH of biofilm while ensuring the balance of the beneficial bacteria are not affected based on our microbiome studies. Finally, I will present work on a sensitive array of nanoparticles designed to identify bacteria in a mixture of oral microbiota using a ‘machine-learning’ driven approach. Throughout these works, I demonstrated how manipulation of chemistry will govern the materials property outcome.

I will then share the advances I made in using nanoparticles for the targeted detection of bone microcracks in vivo using an advanced ‘colored’ computed tomography (photon-counting spectral CT) method and fluorescence imaging for revealing the anatomy of microdamages (Advanced functional materials 2019, ACS applied materials & Interfaces 2018).

I will then proceed with elaborating on the potential of these nanoparticles as inherently therapeutic agents in combating cancer using light and/or radiation (ACS applied materials & Interfaces 2018, Small 2016).

Finally, I will share a sneak peek of my current research on translating nanoparticle technology to advanced human pluripotent stem cell cancer vaccines.

I envision that nanoparticles offer huge opportunities in packing ‘imaging’ and ‘therapy’ capabilities into a single small platform to address critical biomedical problems and will surely overcome their barriers in their translation into the clinic and extend the realm of medicine in the foreseeable future.

Personal Statement and Future Directions:

I received my BSc (2012) and first MSc (2014) in Materials Science and Engineering from Sharif University of Technology and then obtained an MS (2015) and Ph.D. (2019) in Bioengineering from the University of Illinois Urbana Champaign under the supervision of Prof. Dipanjan Pan as AHA predoctoral fellow. After a brief time as an interim Beckman Institute postdoctoral fellow at UIUC, I moved to Stanford University (mentored by Prof. Joseph C Wu and Prof. Sarah Heilshorn) as NIH T32 NRSA postdoctoral fellow where I am making exciting progress on engineering stem cell cancer vaccines.

My long-term goal in research is to achieve comprehensive solutions to biomedical challenges via fundamentally engineering biomaterials/ nanomaterials demonstrating the enormous potential for mimicking the in vivo conditions.

I plan to establish an independent and self-sustaining research program that will build upon my past research experience in biomaterials/ nanomaterials chemistry design, precision medicine, and multimodal imaging. My lab will drive engineering advances in nanoparticles and will explore their potential in three major areas in women’s health of (a) antibiofilm and antiviral platforms against gynecological problems, (b) endometriosis fibrosis immunotherapy, and (c) data-driven nanotoxicology approaches based on in-dish fetal models for predicting child development. These efforts will entail a highly interdisciplinary innovation spanning from designing bio/nanomaterials to preclinical testing in animals and computational in silico investigation.

Complete list of published work is accessible here:

https://scholar.google.com/citations?user=yJyfuU8AAAAJ&hl=en

Teaching Interests:

My teaching philosophy and methods are drawn from (1) my own experience as a student across two countries, (2) actively mentoring undergraduate and graduate-level researchers and learning mentoring skills through targeted programs such as Undergraduate Research Apprentice Program (URAP), and Illinois Scholar Undergrad Program, and (3) by teaching and lecturing as guest speakers at UIUC and Stanford University. In this regard, computers have paved the path for teachers to a great extent. I would like to make my teaching tangible by demonstrating the course lectures in the context of movies, animation and real- life examples. On the other side, my teaching will be combined with research tasks that need to be completed outside the classroom. This includes the creative writing assignment based on a case study which would cultivate independent learning and critical thinking.

Not only do I find the experience of teaching stimulating, but also, I would like to share my knowledge via mentoring the students in the research lab. I have previously leveraged this skill by mentoring 10 undergrad students and a grad student and educating myself by participating in mentorship-building-programs offered by the university. Moreover, I have been TA for the ‘capstone project’ class and have taught mini-lectures in the ‘imaging and therapeutic’ course in MEng program.

As far as my specific teaching interest is concerned, I am qualified to teach the core undergraduate and graduate courses in Bioengineering/Chemical engineering/Materials Science especially with a focus on nanomaterials e.g transport phenomena, kinetics, thermodynamics, etc. I would also envision to develop two courses on the 1) principles of nanotechnology and 2) Nanotheranostics. Principles of nanotechnology course would deal with the concept of nano, why nano matters, types of nanomaterials (nanoparticles, nanocomposites, etc), the principles of nanoparticle formation, basic crystallographic unit cells, kinetics of nanoparticles formation, introduction to organic and inorganic nanomaterials, application of nanomaterials with focus on nanomedicine. Through this class, undergraduate students with minimal information on the basics of nanomaterials would develop a grasp of the nanoworld.

The second course I propose to be incorporated in the curriculum is Nanotheranostics which will focus on the introduction to various imaging modalities and essential rile of nanoprobes for the early diagnosis of the diseases.

Having mentored undergrads in laboratory skills, I am also excited to teach laboratory courses in addition to lecture courses.

In summary, teaching and interacting with students will be an exciting and rewarding aspect of my career. I believe that teaching is not a unidirectional conveyance of information and skills, but that both my students and I will learn and grow through this process.